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Related Experiment Video

Updated: Jul 16, 2025

Detection of Retrotransposition Activity of Hot LINE-1s by Long-Distance Inverse PCR
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Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.

Martin S Taylor1, Connie Wu1,2, Peter C Fridy3

  • 1Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.

Cancer Discovery
|September 12, 2023
PubMed
Summary

A novel protein, Long INterspersed Element-1 open reading frame 1 protein (ORF1p), shows promise as a highly specific, ultrasensitive blood biomarker for early detection and monitoring of multiple cancers.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biomarker Discovery

Background:

  • Improved cancer biomarkers are crucial for early detection, risk stratification, and treatment monitoring.
  • Current protein biomarkers often lack sufficient sensitivity or specificity.
  • Long INterspersed Element-1 open reading frame 1 protein (LINE-1 ORF1p) is overexpressed in various cancers but not in normal tissues.

Purpose of the Study:

  • To investigate the potential of LINE-1 ORF1p as a highly specific, blood-based cancer biomarker.
  • To develop ultrasensitive assays for detecting ORF1p in plasma.
  • To evaluate ORF1p's utility in early cancer detection and treatment monitoring.

Main Methods:

  • Engineered ultrasensitive digital immunoassays capable of detecting mid-attomolar concentrations of ORF1p.
  • Measured plasma ORF1p levels in patients with various cancers.
  • Assessed ORF1p performance in early detection, diagnostic panels, and treatment response monitoring.

Main Results:

  • Ultrasensitive assays detected ORF1p in plasma across multiple cancers with high specificity.
  • Plasma ORF1p demonstrated potential for early ovarian cancer detection.
  • ORF1p improved diagnostic performance in multianalyte panels and enabled early monitoring of treatment response in gastroesophageal cancers.
  • ORF1p showed prognostic value for overall survival in gastroesophageal and colorectal cancers.

Conclusions:

  • LINE-1 ORF1p is a promising multicancer biomarker detectable in blood.
  • Ultrasensitive ORF1p assays offer a novel, rapid, and cost-effective tool for cancer detection and monitoring.
  • ORF1p has potential utility for disease detection, risk stratification, and monitoring treatment response across various carcinomas.